The present invention is directed to a method for enhancing the relining of a blood vessel by use of an endothelial cell (EC) mitogen. This method is particularly useful for reendothelialization of an injured blood vessel.
Atherosclerosis, a common form of arteriosclerosis, results from the development of an intimal lesion and subsequent narrowing of the vessel lumen. As the lesions increase in size, they reduce the diameter of the arteries and impede blood circulation.
Many therapeutical alternatives have been considered for the treatment of atherosclerosis, including surgery and medical treatment. One potential therapy is percutaneous transluminal angioplasty (balloon angioplasty). In balloon angioplasty, a catheter equipped with an inflatable balloon is threaded intravascularly to the site of the atherosclerotic narrowing of the vessel. Inflation of the balloon compresses the plaque enlarging the vessel.
While such angioplasty has gained wider acceptance, it suffers from two major problems, i.e., abrupt closure and restenosis. Abrupt closure refers to the acute occlusion of a vessel immediately after or within the initial hours following a dilation procedure. Abrupt closure occurs in approximately one in twenty cases and frequently results in myocardial infarction and death if blood flow is not restored in a timely manner.
Restenosis refers to the re-narrowing of an artery after an initially successful angioplasty. Restenosis of the blood vessel is thought to be due to injury to the endothelial cells of the blood vessel during angioplasty, or during inflation of the balloon catheter. During healing of the blood vessel after surgery, smooth muscle cells proliferate faster than endothelial cells narrowing the lumen of the blood vessel, and starting the atherosclerotic process anew. In recent years, smooth muscle cell proliferation has been recognized as a major clinical problem limiting the long-term efficacy of percutaneous transluminal coronary angioplasty.
In an effort to prevent restenosis of the treated blood vessel, the search for agents that can reduce or prevent excessive proliferation of smooth muscle cells have been the object of much research. (The occurrence and effects of smooth muscle cell proliferation after these types of surgery have been reviewed, for example, in Ip, et al., (June 1990) J. Am. College of Cardiology 15:1667-1687, and Faxon, et al. (1 987) Am. J. of Cardiology 60: 5B-9B.)
An alternative to prevent problems associated with angioplasty, places endovascular stents in the dilated segments to mechanically block abrupt closure and restenosis. Unfortunately, the use of such stents are limited by direct (subacute thrombosis) or indirect (bleeding, peripheral vascular complications) complications. After stent implantation the patients are threatened with stent thrombosis until the struts of the stent are covered by endothelium. Thus, an aggressive therapy using anticoagulation and/or antiplatelet agents is necessary during this period of time. While these therapies are able to decrease the rate of stent thrombosis, they are the main source of indirect complications.
Thus, the need for a simple and effective means to reduce restenosis is extremely important.